Chronic kidney disease caused by maternally inherited diabetes and deafness: a case report.

Maternally inherited diabetes and deafness (MIDD) is a mitochondrial genetic disorder with variable clinical presentations, which can delay its diagnosis. Herein, we report the case of a 57-year-old Japanese man with MIDD who developed chronic kidney disease. He developed proteinuria long before his diabetes and deafness; at the age of 36 years, a renal biopsy showed minor glomerular abnormality and electron microscopy showed mild mitochondrial degeneration in the distal tubular epithelial cells. Twenty years later, a second renal biopsy showed nephrosclerosis with interstitial fibrosis and arteriolar hyaline thickening, despite the absence of hypertension and relatively good glycemic control. Granular swollen epithelial cells were found in the medullary collecting duct epithelium. Electron microscopy showed accumulating mitochondria in podocytes and tubular cells, leading to the diagnosis of MIDD. A muscle biopsy also showed ragged-red fibers, despite the absence of muscle weakness. Mitochondrial DNA analysis revealed an m.3243A > G mutation, and taurine supplementation was initiated. Our findings suggest that mitochondrial dysfunction is mainly associated with progressive renal damage.

A comparative analysis of hydrosilative amide reduction catalyzed by first-row transition metal (Mn, Fe, Co, and Ni) N-phosphinoamidinate complexes.

A comparative study of the performance of (PN)M(N(SiMe3)2) (M = Mn, Fe, Co, and Ni) pre-catalysts supported by N-phosphinoamidinate ligation, as well as M(N(SiMe3)2)n (M = Li, Na, K, Mn, Fe, and Co) pre-catalysts, in the hydrosilative reduction of selected tertiary amide test substrates using PhSiH3 is reported. Encouraged by the performance observed herein for (PN)Ni(N(SiMe3)2) in the reduction of both N,N-dibenzylbenzamide and N,N-diisopropylbenzamide, further competitive testing involving the known complex (PN)Ni(NHdipp) (dipp = 2,6-diisopropylphenyl), as well as the new and crystallographically characterized mononuclear complexes (PN)Ni(OR) (R = 2,6-dimethylphenyl or tBu), revealed (PN)Ni(OtBu) to be particularly effective in such reduction chemistry, including transformations involving the secondary amides N-benzylbenzamide and caprolactam.

Seasonal variation in hemodialysis initiation: A single-center retrospective analysis.

The number of new dialysis patients has been increasing worldwide, particularly among elderly individuals. However, information on seasonal variation in hemodialysis initiation in recent decades is lacking, and the seasonal distribution of patients' conditions immediately prior to starting dialysis remains unclear. Having this information could help in developing a modifiable approach to improving pre-dialysis care. We retrospectively investigated the records of 297 patients who initiated hemodialysis at Hiroshima Prefectural Hospital from January 1st, 2009 to December 31st, 2013. Seasonal differences were assessed by χ2 or Kruskal-Wallis tests. Multiple comparison analysis was performed with the Steel test. The overall number of patients starting dialysis was greatest in winter (n = 85, 28.6%), followed by spring (n = 74, 24.9%), summer (n = 70, 23.6%), and autumn (n = 68, 22.9%), though the differences were not significant. However, there was a significant winter peak in dialysis initiation among patients aged ≥65 years, but not in those aged <65 years. Fluid overload assessed by clinicians was the most common uremic symptom among all patients, but a winter peak was only detected in patients aged ≥65 years. The body weight gain ratio showed a similar trend to fluid overload assessed by clinicians. Pulmonary edema was most pronounced in winter among patients aged ≥65 years compared with other seasons. The incidences of infection were modestly increased in summer and winter, but not statistically significant. Cardiac complications were similar in all seasons. This study demonstrated the existence of seasonal variation in dialysis initiation, with a winter peak among patients aged ≥65 years. The winter increment in dialysis initiation was mainly attributable to increased fluid overload. These findings suggest that elderly individuals should be monitored particularly closely during the winter.

Low coordinate iron derivatives stabilized by a ß-diketiminate mimic. Synthesis and coordination chemistry of enamidophosphinimine scaffolds to generate diiron dinitrogen complexes.

In an effort to mimic N-diaryl-ß-diketiminate ligands (Nacnac), we have converted N-arylimine phosphine ligands to enamine-phosphinimines via the Staudinger reaction. By varying the aryl azide, one can access enamine-phosphinimine ligands with the same or different N-aryl substituents on both the enamine and phosphinimine units, which allows this intrinsically unsymmetrical bidentate donor set to present variable steric effects at the metal center. The enamine-phosphinimine was deprotonated and used in metathetical reactions with Fe(ii) bromide precursors to generate low coordinate complexes of the empirical formula [(CY5)NpN(Ar,Ar')]FeBr (where CY5 = cyclopentenyl; Ar,Ar' = 2,6-diisopropylphenyl, 2,6-dimethylphenyl, 2,4,6-trimethylphenyl). Depending on the substituents, these bromide derivatives can be monomeric or dimeric via bromide bridges. Reduction under dinitrogen using potassium graphite generates the dinitrogen complexes ([(CY5)NpN(Ar,Ar')]Fe)2(µ-N2) for Ar,Ar' = 2,6-diisopropylphenyl, and Ar = 2,6-dimethylphenyl, Ar' = 2,4,6-trimethylphenyl. However, for the former, a unsymmetrical side product can be isolated that has a bridging N-2,6-diisopropylphenylimide unit with one enamido-phosphine ligand bound to one iron and the other iron stabilized with an intact enamido-phosphinimine. When the steric bulk is reduced on both nitrogen donors, a complicated product mixture is obtained after reduction from which a small amount of [(CY5)NpN(Ar,Ar')]Fe[(CY5)NP(Ar)] (Ar,Ar' = 2,6-dimethylphenyl) could be isolated. All of these complexes are paramagnetic and have been characterized by elemental analysis, magnetic studies and X-ray crystallography.

N2 activation by an iron complex with a strong electron-donating iminophosphorane ligand.

A new tridentate cyclopentane-bridged iminophosphorane ligand, N-(2-diisopropylphosphinophenyl)-P,P-diisopropyl-P-(2-(2,6-diisopropylphenylamido)cyclopent-1-enyl)phosphoranimine (NpNPiPr), was synthesized and used in the preparation of a diiron dinitrogen complex. The reaction of the iron complex FeBr(NpNPiPr) with KC8 under dinitrogen yielded the dinuclear dinitrogen Fe complex [Fe(NpNPiPr)]2(µ-N2), which was characterized by X-ray analysis and resonance Raman and NMR spectroscopies. The X-ray analysis revealed a diiron complex bridged by the dinitrogen molecule, with each metal center coordinated by an NpNPiPr ligand and dinitrogen in a trigonal-monopyramidal geometry. The N­N bond length is 1.184(6) Å, and resonance Raman spectra indicate that the N­N stretching mode ν(14N2/15N2) is 1755/1700 cm­1. The magnetic moment of [Fe(NpNPiPr)]2(µ-N2) in benzene-d6 solution, as measured by 1H NMR spectroscopy by the Evans method, is 6.91µB (S = 3). The Mössbauer spectrum at 78 K showed δ = 0.73 mm/s and ΔEQ = 1.83 mm/s. These findings suggest that the iron ions are divalent with a high-spin configuration and that the N2 molecule has (N═N)2­ character. Density functional theory calculations performed on [Fe(NpNPiPr)]2(µ-N2) also suggested that the iron is in a high-spin divalent state and that the coordinated dinitrogen molecule is effectively activated by π back-donation from the two iron ions (dπ) to the dinitrogen molecule (πx* and πy*). This is supported by cooperation between a large negative charge on the iminophosphorane ligand and strong electron donation and effective orbital overlap between the iron dπ orbitals and N2 π* orbitals supplied by the phosphine ligand.

Cleavage of an aryl carbon-nitrogen bond of a phosphazido iron(II) complex promoted by hydride metathesis.

Upon reaction with KBEt3H, the pseudo tetrahedral Fe(II) complex with a bulky enamido-phosphazide ligand set undergoes elimination of N2 and 1,3-Me2C6H4 to generate the dinuclear Fe(II) derivative with bridging phosphinimido units. When the reaction is performed using KBEt3D, no deuterium is incorporated into the eliminated 1,3-Me2C6H4; all of the deuterium ends up as D2. When the reaction is performed in THF-d8, only 2-d-1,3-Me2C6H3D was detected by GCMS. These studies are consistent with a radical mechanism.

Hemodialysis immediately after cardiac catheterization is a risk factor for intradialytic hypotension.

Many hemodialysis clinicians have noticed that patients frequently develop intradialytic hypotension (IDH) immediately after cardiac catheterization (CC). However, precise data about the incidence of IDH immediately after CC are scarce. This study involved a single-center, retrospective, cross-sectional design. We reviewed the medical records of all HD patients who underwent CC between January 2009 and March 2012 at Hiroshima Prefectural Hospital. IDH was defined as a fall of systolic blood pressure of more than 20 mm Hg or a fall of mean blood pressure of more than 10 mm Hg, with symptoms according to the K/DOQI criteria. Data on a total of 112 patients were obtained: 64 patients commenced HD immediately after CC (IA group) and 48 patients underwent HD on the day after CC (ND group). The overall incidence of IDH was 34% (38/112). The incidence of IDH was significantly higher in the IA group than in the ND group (27/64, 42% vs. 11/48, 23%; P < 0.05). Multivariate logistic regression analysis showed that IA (odds ratio, 5.39; 95% confidence interval, 1.76 to 16.49; P < 0.01), coronary stenosis (odds ratio, 4.16; 95% confidence interval, 1.49 to 11.64; P < 0.05) were independently associated with IDH. This study revealed that HD immediately after CC is associated with a higher incidence of IDH. Clinicians should consider that HD following CC be scheduled for the next day, especially in patients with coronary stenosis.

Successful treatment with plasma exchange for ANCA-negative pauci-immune crescentic glomerulonephritis with D-negative hemolytic uremic syndrome.

Co-existence of antineutrophil cytoplasmic antibody (ANCA)-negative pauci-immune crescentic glomerulonephritis (CGN) and thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTPHUS) is extremely rare and has a poor renal prognosis. We report a 76-year-old female that had both ANCA and anti-human lysosomal membrane protein 2 (LAMP-2) antibody-negative pauci-immune CGN with D-negative HUS. She was admitted with proteinuria and worsening renal failure with massive crescent formation on renal biopsy specimens. We initiated intravenous methylprednisolone pulse therapy followed by oral prednisolone, but she still developed D-negative HUS. We then initiated plasma exchange, which achieved remission of D-negative HUS and improved renal function. To our knowledge, this is the first report of recovery from renal failure in ANCA-negative pauci-immune CGN with TTP-HUS.

Do rural and remote areas really have limited accessibility to health care? Geographic analysis of dialysis patients in Hiroshima, Japan.

INTRODUCTION: For an equitable distribution of health resources, resource-allocation policies focus on rural and also remote areas, assuming that these areas are underserved. However, definitions of 'rural' and 'remote' vary, and are not necessarily synonymous with 'underserved'. This Japanese study evaluated the association between the rurality/remoteness of the community in which a patient lives and his/her geographic accessibility to dialysis facilities. METHODS: Based on 1867 communities (census blocks) in Hiroshima Prefecture, Japan, predictive powers of five community-level rural/remote parameters (population size, population density, elderly rate, agriculture rate, and distance to the nearest city) were evaluated to identify communities where dialysis patients had a longer commute time to dialysis facilities. The proportion of low-access communities was examined when those communities were merged to form larger geographic units (four-level stepwise merger). One-way driving times of dialysis patients were used as the access parameter of a community and were calculated using geographic information systems based on the addresses of all the 7374 patients certified by municipalities as having renal disability, and on the addresses and capacities of all 98 dialysis facilities in Hiroshima. RESULTS: The average driving time was negatively correlated with population and population density, and positively correlated with elderly rate, agriculture rate, and distance to nearest city. When low-access was defined as >20, >30 & >40 min driving time, all rural/remote parameters showed better sensitivities (range 63.5-94.9%) than specificities (55.2-77.9%) to identify low-access communities, and positive predictive values were less than 50% for most parameters. When low-access was defined as >30 min driving time, the proportion of low-access communities substantially decreased when the geographic unit was expanded. In the administrative 'rural' area, the largest geographic unit, the percentage of low-access communities was 30%. CONCLUSIONS: In any definition of 'rural/remote', and in any definition of 'low-access', the rural/remote areas contain a substantial proportion of high-access communities. In addition, a substantial proportion of low-access communities was excluded from rural/remote areas. The accuracy of the term 'low-access' deteriorated when the geographic unit of analysis was expanded. In order to identify underserved areas precisely, it is necessary to set the geographic unit of analysis as small as possible and measure the geographic accessibility itself, rather than designate some areas as 'rural' or 'remote', based on conventional geographic/demographic/distance parameters.

Preparation, characterization, and reactivity of dinitrogen molybdenum complexes with bis(diphenylphosphino)amine derivative ligands that form a unique 4-membered P-N-P chelate ring.

Five dinitrogen-molybdenum complexes bearing bis(diphenylphosphino)amine derivative ligands (L(R)) that form a unique 4-membered P-N-P chelate ring, trans-[Mo(N(2))(2)(L(R))(2)] (2(R): R = Ph, Xy, p-MeOPh, 3,5-iPr(2)Ph, iPr), were prepared for the purpose of binding a dinitrogen molecule. The corresponding two dichloride-molybdenum complexes, trans-[MoCl(2)(L(R))(2)] (1(R): R = Ph, Xy), were also prepared as comparisons. FT-IR spectra of 2(R) were measured and compared the ν(N≡N) values. Moreover, X-ray crystal structure determination of 1(R) (R = Ph, Xy) and 2(R) (R = Xy, 3,5-iPr(2)Ph) is performed. These experimental results indicated that the coordinated dinitrogen molecule gets easily influenced by the N-substitutent of diphosphinoamine ligand. In addition, to investigate the effect of the properties of the diphosphinoamine ligand for the dinitrogen molybdenum complexes, we performed DFT calculations that focused on the difference of N-substituent, the dihedral angle between P-N-P plane and N-substituent aryl group, and the P-N-P bite angle. This calculation revealed that the competition between the back-donation from metal to dinitrogen and that from metal to ligand was affected by P-N-P bite angle and the dihedral angle of N-substituent of ligand. In order to examine the reactivity with respect to conversion of dinitrogen to ammonia, protonation and trimethylsilylation reactions of the coordinated dinitrogens were carried out for 2(R).

The impact of travel time on geographic distribution of dialysis patients.

BACKGROUNDS: The geographic disparity of prevalence rates among dialysis patients is unclear. We evaluate the association between travel time to dialysis facilities and prevalence rates of dialysis patients living in 1,867 census areas of Hiroshima, Japan. Furthermore, we study the effects of geographic features (mainland or island) on the prevalence rates and assess if these effects modify the association between travel time and prevalence. METHODS: The study subjects were all 7,374 people that were certified as the "renal disabled" by local governments in 2011. The travel time from each patient to the nearest available dialysis facility was calculated by incorporating both travel time and the capacity of all 98 facilities. The effect of travel time on the age- and sex-adjusted standard prevalence rate (SPR) and 95% confidence intervals (CIs) at each census area was evaluated in two-level Poisson regression models with 1,867 census areas (level 1) nested within 35 towns or cities (level 2). The results were adjusted for area-based parameters of socioeconomic status, urbanity, and land type. Furthermore, the SPR of dialysis patients was calculated in each specific subgroup of population for travel time, land type, and combination of land type and travel time. RESULTS: In the regression analysis, SPR decreased by 5.2% (95% CI: -7.9--2.3) per 10-min increase in travel time even after adjusting for potential confounders. The effect of travel time on prevalence was different in the mainland and island groups. There was no travel time-dependent SPR disparity on the islands. The SPR among remote residents (>30 min from facilities) in the mainland was lower (0.77, 95% CI: 0.71-0.85) than that of closer residents (≤ 30 min; 0.95, 95% CI: 0.92-0.97). CONCLUSIONS: The prevalence of dialysis patients was lower among remote residents. Geographic difficulties for commuting seem to decrease the prevalence rate.

The impact of rural hospital closures on equity of commuting time for haemodialysis patients: simulation analysis using the capacity-distance model.

BACKGROUND: Frequent and long-term commuting is a requirement for dialysis patients. Accessibility thus affects their quality of lives. In this paper, a new model for accessibility measurement is proposed in which both geographic distance and facility capacity are taken into account. Simulation of closure of rural facilities and that of capacity transfer between urban and rural facilities are conducted to evaluate the impacts of these phenomena on equity of accessibility among dialysis patients. METHODS: Post code information as of August 2011 of all the 7,374 patients certified by municipalities of Hiroshima prefecture as having first or third grade renal disability were collected. Information on post code and the maximum number of outpatients (capacity) of all the 98 dialysis facilities were also collected. Using geographic information systems, patient commuting times were calculated in two models: one that takes into account road distance (distance model), and the other that takes into account both the road distance and facility capacity (capacity-distance model). Simulations of closures of rural and urban facilities were then conducted. RESULTS: The median commuting time among rural patients was more than twice as long as that among urban patients (15 versus 7 minutes, p<0.001). In the capacity-distance model 36.1% of patients commuted to the facilities which were different from the facilities in the distance model, creating a substantial gap of commuting time between the two models. In the simulation, when five rural public facilitiess were closed, Gini coefficient of commuting times among the patients increased by 16%, indicating a substantial worsening of equity, and the number of patients with commuting times longer than 90 minutes increased by 72 times. In contrast, closure of four urban public facilities with similar capacities did not affect these values. CONCLUSIONS: Closures of dialysis facilities in rural areas have a substantially larger impact on equity of commuting times among dialysis patients than closures of urban facilities. The accessibility simulations using the capacity-distance model will provide an analytic framework upon which rational resource distribution policies might be planned.

[N-terminal pro brain natriuretic peptide predicts hospitalization of hemodialysis patients for cardiovascular disease].

We investigated whether or not N-terminal pro brain natriuretic peptide (NT-proBNP) could predict hospitalization for cardiovascular disease (CVD) among Japanese hemodialysis patients. A total of 104 patients on maintenance dialysis 3 times per week were enrolled. We followed the patients for 23.9 +/- 4.2 months and 19 hospitalizations for CVD occurring during this period. The area under the curve (AUC) for the risk of CVD hospitalization was calculated after drawing a receiver operating characteristic curve. Predialysis NT-proBNP showed a larger AUC value than both postdialysis NT-proBNP and brain natriuretic peptide. The optimal cut-off value of predialysis NT-proBNP for predicting CVD hospitalization was 5,894 pg/mL, (sensitivity of 60 % and specificity of 76 %). Diabetes mellitus, a history of CVD, and the predialysis NT-proBNP level were significant determinants of CVD hospitalization according to Cox proportional hazards analysis. In conclusion, predialysis NT-proBNP is useful for predicting CVD hospitalization in hemodialysis patients.

15-Deoxy-Delta12,14-prostaglandin J2 inhibits angiotensin II-induced fibronectin expression via hepatocyte growth factor induction in human peritoneal mesothelial cells.

15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an endogenous peroxisome proliferator-activated receptor gamma (PPARgamma) agonist that suppresses progressive matrix deposition; however, little is known about the effects of 15d-PGJ(2) on human peritoneal mesothelial cells (HPMCs). We investigated the following: (i) the expression of PPARgamma; (ii) the effect of 15d-PGJ(2) on angiotensin II (Ang II)-induced fibronectin (FN) expression and secretion; (iii) the effect of 15d-PGJ(2) (with or without Ang II and with or without the specific PPARgamma antagonist GW9662) and pioglitazone, a synthetic PPARgamma agonist, on hepatocyte growth factor (HGF) expression and secretion; (iv) the effect of HGF on Ang II-induced FN expression and secretion; (v) the expression of c-Met (a specific HGF receptor) and its phospho-signal; and (vi) the involvement of HGF in the effect produced by 15d-PGJ(2) using selective c-Met inhibitor PHA-665752. The presence of PPARgamma was detected by western blot analysis. 15d-PGJ(2) inhibited Ang II-induced FN expression and increased HGF expression, even in the presence of Ang II. This effect of HGF expression was completely prevented by co-treatment with GW9662. Additionally, upregulation of HGF secretion induced by 15d-PGJ(2) and HGF production induced by pioglitazone was revealed. We demonstrated the presence of c-Met, and presented evidence that HGF inhibits Ang II-induced FN expression and activates phosphorylation of c-Met, which is blocked by PHA-665752; 15d-PGJ(2) also activated c-Met phosphorylation. Furthermore, PHA-665752 attenuates the inhibitory effects of 15d-PGJ(2) on FN secretion. These findings suggest that 15d-PGJ(2) has a novel and potent antifibrotic effect in HPMC and this action is likely mediated by HGF.

Erratum: Tetra-chlorido[(diphenyl-phosphino)diphenyl-phosphine oxide-κO]zirconium(IV) benzene monosolvate. Corrigendum.

The chemical name of the title compound in the paper by Ogawa, Kajita & Masuda [Acta Cryst. (2009), E65, m1129] is corrected.[This corrects the article DOI: 10.1107/S1600536809031882.].

Synthesis and characterization of a benzene-dimolybdenum complex with a new bridging mode.

A novel dimolybdenum complex, [Mo(2)(((i)Pr)L')(2)(C(6)H(6))] (1(C(6)H(6))), has been synthesized and characterized as a benzene-ring-bridged dimolybdenum complex with a cis-mu-eta(2)(1,2):eta(2)(4,5) binding mode. Complex 1(C(6)H(6)) reacts with MeMgBr to form 2, where mu-benzene is methylated to form mu-xylene.

C-C chemokine receptor 2 expression by circulating monocytes influences atherosclerosis in patients on chronic hemodialysis.

Mortality from cardiovascular or cerebrovascular disease due to atherosclerosis is increased in patients on chronic hemodialysis. Monocyte chemoattractant protein-1 and its receptor, C-C chemokine receptor 2, play an important role in recruiting monocytes to atherosclerotic lesions. The relationship between atherosclerosis in hemodialysis patients and C-C chemokine receptor 2 expression is unknown. Fifty-six patients on chronic hemodialysis and 27 age- and sex-matched controls were enrolled. Serum levels of monocyte chemoattractant protein-1 and expression of C-C chemokine receptor 2 by circulating monocytes were determined. Atherosclerosis was evaluated from the carotid intima-media thickness and cardio-ankle vascular index. Serum levels of monocyte chemoattractant protein-1 and expression of C-C chemokine receptor 2 by monocytes were significantly higher in the hemodialysis patients than the controls. Multiple regression analysis showed a positive correlation between receptor expression and both indexes of atherosclerosis. C-C chemokine receptor 2 expression by circulating monocytes influences atherosclerosis in patients on chronic hemodialysis.

Tetra-chlorido[(diphenyl-phosphino)diphenyl-phosphine oxide-κO]zirconium(IV) benzene monosolvate.

In the title centrosymmetric mononuclear Zr(IV) compound, [ZrCl(4){P(O)(C(6)H(5))(2)P(C(6)H(5))(2)}(2)]·C(6)H(6), the central Zr(IV) ion is coordinated by two O atoms from two symmetry-related (diphenyl-phosphino)diphenyl-phosphine ligands and four Cl atoms in a distorted octahedral geometry with the four Cl atoms in the equatorial positions. The mol-ecule lies about a center of inversion and the benzene solvent mol-ecule about another center of inversion. The P=O bond [1.528 (2) Å] is slightly longer than a typical P=O double bond (average 1.500 ).

An oral adsorbent, AST-120, combined with a low-protein diet and RAS blocker, for chronic kidney disease.

BACKGROUND: A low-protein diet and treatment with renin-angiotensin system (RAS) blockers can delay the progression of chronic kidney disease (CKD). The oral adsorbent AST-120 (Kremezin) has a renoprotective effect by reducing serum levels of uremic toxins. We investigated the influence of AST-120 on the preservation of renal function in patients with CKD. METHODS: Twenty-eight patients were randomized to 2 groups: 15 patients receiving 6.0 g of AST-120 daily for 12 months plus a low-protein diet and RAS blocker therapy (group A) and 13 patients who were not given AST-120 (group B). All of them had shown progressive deterioration of renal function with basal treatment. Mean baseline serum creatinine level (+/- standard deviation) was 2.4 +/- 0.8 mg/dL in group A and 2.7 +/- 0.8 mg/dL in group B. There were no significant differences in background parameters before AST-120 therapy. RESULTS: The change in the estimated glomerular filtration rate (eGFR) was significantly smaller in group A than in group B. The change was also significantly smaller in patients with a baseline serum creatinine <2.4 mg/dL and in patients with rapid progression. After 12 months, the slope of the eGFR curve was significantly less steep compared with baseline in group A (-1.77 vs. -0.52 ml/min per month), but there was no significant change in group B. The slope was also significantly less steep in patients with rapid progression. CONCLUSIONS: Adding AST-120 to a low-protein diet and RAS blocker therapy may delay the deterioration of chronic renal failure, especially in patients with early or rapid progression.

TNF-alpha-inducing protein, a carcinogenic factor secreted from H. pylori, enters gastric cancer cells.

TNF-alpha inducing protein (Tip alpha) is secreted from Helicobacter pylori (H. pylori): it is a potent inducer of TNF-alpha and chemokine genes, mediated through NF-kappaB activation, and it also induces tumor-promoting activity in Bhas 42 cells. To investigate the carcinogenic mechanisms of H. pylori with Tip alpha, we first examined how Tip alpha acts on gastric epithelial cells. We found that fluorescent-Tip alpha specifically bound to, and then entered, the cells in a dose- and temperature-dependent manner, whereas deletion mutant of Tip alpha (del-Tip alpha), an inactive form, neither bound to nor entered the cells, suggesting the presence of a specific binding molecule. Mutagenesis analysis of Tip alpha revealed that a dimer formation of Tip alpha with a disulfide bond is required for both specific binding and induction of TNF-alpha gene expression. A confocal laser scanning microscope revealed some Tip alpha in the nuclei, but del-Tip alpha was not present, which indicated that an active form of Tip alpha can penetrate the nucleus and may be involved in the induction of TNF-alpha gene expression. Examination of Tip alpha production and secretion in 28 clinical isolates revealed that H. pylori obtained from gastric cancer patients secreted Tip alpha in significantly higher amounts than did H. pylori from patients with chronic gastritis, suggesting that Tip alpha is an essential factor in H. pylori inflammation and cancer microenvironment in the human stomach. Tip alpha is thus a new carcinogenic factor of H. pylori that can enter the nucleus through a specific binding molecule, and its mechanism of action is completely different from that of CagA.